Systemic administration of medication, nutrition, or other substances into the circulatory system affects the entire body. Systemic routes of administration include enteral (e.g., oral dosage resulting in absorption of the drug through the gastrointestinal tract) and parenteral (e.g., intravenous, intramuscular, and subcutaneous injections) administration. Administration of immunotherapeutics typically relies on these systemic administration routes. However, immunotherapeutics often induce toxicities that are undesirable for non-diseased tissues, thus systemic administration can lead to unwanted side effects. In some instances, certain promising therapeutics are extremely difficult to develop due to associated toxicities and the limitations of current administration methods and systems. For example, systemic administration of immunotherapeutic agents for the treatment of cancer is often associated with immune-related adverse events (e.g., skin rashes, hepatitis, diarrhea, colitis, hypophysitis, thyroiditis, and adrenal insufficiency). These adverse events may in part be attributable to the exposure of non-tumor-specific immune cells to drug, as well as the higher doses required by systemic adminstration to achieve sufficient concentration in the tumor to induce a desired response. In addition to enhancing safety, localizing delivery of immunotherapeutic agents can improve efficacy by concentrating the action of the drug where it is needed.
Surgery is often the first-line of treatment for solid tumor cancers and is generally used in combination with systemic administration of anti-cancer therapy. However, surgery-induced immunosuppression has been implicated in the development of postoperative septic complications and tumor metastasis due to changes in a variety of metabolic and endocrine responses, ultimately resulting in the death of many patients (Smyth, M. J. et al. Nature Reviews Clinical Oncology, 2016, 13, 143-158). Accordingly, there is a need to effectively and safely administer immunotherapies in combination with surgical approaches to achieve antimetastatic efficacy and reduction in tumor regrowth.